(±)-Salvicatone A: A Pair of C27-Meroterpenoid Enantiomers with Skeletons from the Roots and Rhizomes of Salvia castanea Diels f. tomentosa Stib.

(±)-Salvicatone A (1), a C27-meroterpenoid featuring a unique 6/6/6/6/6-pentacyclic carbon skeleton with a 7,8,8a,9,10,10a-hexahydropyren-1 (6H)-one motif, was isolated from the roots and rhizomes of Salvia castanea Diels f. tomentosa Stib. Its structure was characterized by comprehensive spectroscopic analyses along with computer-assisted structure elucidation, including ACD/structure elucidator and quantum chemical calculations with 1H/13C NMR and electronic circular dichroism. Biogenetically, compound 1 was constructed from decarboxylation following [4 + 2] Diels-Alder cycloaddition reaction between caffeic acid and miltirone analogue. Bioassays showed that (-)-1 and (+)-1 inhibited nitric oxide production in lipopolysaccharide-induced RAW264.7 macrophage cells with an IC50 value of 6.48 ± 1.25 and 15.76 ± 5.55 µM, respectively. The structure-based virtual screening based on the pharmacophores in ePharmaLib, as well as the molecular docking and molecular dynamics simulations study, implied that (-)-1 and (+)-1 may potentially bind to retinoic acid receptor-related orphan receptor C to exert anti-inflammatory activities.

Short- and long-term outcomes of laparoscopic versus open liver resection for large hepatocellular carcinoma: a propensity score study.

PURPOSE: Laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) remains controversial, especially for tumors larger than 5 cm. We compared the short- and long-term outcomes of laparoscopic and open liver resection (OLR) for large HCC. METHODS: Patients with large HCC after curative hepatectomy were enrolled. To compare the short-term outcomes, propensity score matching (PSM) and inverse probability treatment weighting (IPTW) were performed to reduce the effect of confounding factors, respectively. Subsequently, Cox-regression analyses were conducted to identify the independent risk factors associated with decreased recurrence-free survival (RFS) and poor overall survival (OS). RESULT: There were 265 patients enrolled in the final analysis: 146 who underwent OLR and 119 who underwent LLR. There was no significant difference between the OLR and LLR groups according to PSM and IPTW analysis (all P > 0.05). Multivariable analysis revealed that LLR was not independently associated with poorer OS (HR 1.15, 95% CI 0.80-1.67, P = 0.448) or RFS (HR 1.22, 95% CI 0.88-1.70, P = 0.238). CONCLUSION: There were no significant differences in perioperative complications or long-term prognosis between LLR and OLR for large HCC, which provides evidence for standard laparoscopic surgical practice with adequate surgeon experience and careful patient selection.

Preoperative prediction model for microvascular invasion in HBV-related intrahepatic cholangiocarcinoma.

BACKGROUND AND AIMS: Preoperative prediction of microvascular invasion (MVI) using a noninvasive method remain unresolved, especially in HBV-related in intrahepatic cholangiocarcinoma (ICC). This study aimed to build and validate a preoperative prediction model for MVI in HBV-related ICC. METHODS: Patients with HBV-associated ICC undergoing curative surgical resection were identified. Univariate and multivariate logistic regression analyses were performed to determine the independent risk factors of MVI in the training cohort. Then, a prediction model was built by enrolling the independent risk factors. The predictive performance was validated by receiver operator characteristic curve (ROC) and calibration in the validation cohort. RESULTS: Consecutive 626 patients were identified and randomly divided into the training (418, 67%) and validation (208, 33%) cohorts. Multivariate analysis showed that TBIL, CA19-9, tumor size, tumor number, and preoperative image lymph node metastasis were independently associated with MVI. Then, a model was built by enrolling former fiver risk factors. In the validation cohort, the performance of this model showed good calibration. The area under the curve was 0.874 (95% CI: 0.765-0.894) and 0.729 (95%CI: 0.706-0.751) in the training and validation cohort, respectively. Decision curve analysis showed an obvious net benefit from the model. CONCLUSION: Based on clinical data, an easy model was built for the preoperative prediction of MVI, which can assist clinicians in surgical decision-making and adjuvant therapy.

Association between P-Selectin Autoantibody Positive and Response to Steroid Treatment in Newly Diagnosed Immune Thrombocytopenia Patients.

OBJECTIVE: This study aimed to detect the association between P-selectin autoantibody positive and response to steroid treatment in newly diagnosed immune thrombocytopenia (ITP) patients. METHODS: The data from 105 newly diagnosed adult ITP patients administered with first-line of steroid treatment from October 2016 to May 2021 were retrospectively analyzed. Treatment responses were evaluated within 3 months after the onset of treatment. RESULTS: Among the 105 patients, 80.00% (84/105) of patients presented with platelet glycoprotein-specific antibody positive; 44.76% (47/105) patients were anti-P-selectin positive, while 35.24% (37/105) were anti-P-selectin negative. No significant difference in overall response was observed between patients who were anti-P-selectin positive and those who were anti-P-selectin negative (74.47% vs. 89.19, χ2 = 2.910, p = 0.088). But patients who were anti-P-selectin negative had significantly higher complete response rate, compared to those who were anti-P-selectin positive (72.97% vs. 48.94%, χ2 = 4,965, p = 0.026). Logistic regression analysis revealed that anti-GP IIb/IIIa positive (OR = 3.114, p = 0.010, 95% CI: 1.313-7.388) and anti-P-selectin positive (OR = 0.309, p = 0.036, 95% CI: 0.127-0.753) were two factors that could affect patients' response. CONCLUSIONS: Our study found that ITP patients with anti-GP IIb/IIIa may have a higher response to steroid treatment, but anti-P-selectin-mediated-ITP might be less responsive to steroid treatment. In adults with ITP, the presence of anti-P-selectin autoantibodies is a predictive factor for poor response to steroid treatment.

A thioredoxin peroxidase protects Pieris rapae from oxidative stress induced by chlorantraniliprole exposure.

Chlorantraniliprole (CAP) is an insecticide widely used to control the small white butterfly (SWB), Pieris rapae. Exposure to CAP can cause oxidative injury in SWB; however, it is unclear if antioxidant enzymes are involved in the defense process. In this study, a thioredoxin peroxidase (PrTPX1) gene was identified from SWB by using a homology search method. The gene encoded a 195 amino-acid PrTPX1 protein. Sequence characteristics and phylogenetic analysis indicated that PrTPX1 was a typical "2-Cys" TPX, and the PrTPX1 gene consisted of four exons and three introns. Reverse transcription-quantitative polymerase chain reaction analysis indicated that the messenger RNA levels of PrTPX1 were highest in third-, fourth- and fifth-instar larval stages and in the larval midgut. Treatment with sublethal doses (LD20 and LD50 ) of CAP for 6, 12, 18, and 24 h resulted in increased H2 O2 concentration in SWB larvae, indicating insecticide-induced oxidative stress. The transcriptional levels of PrTPX1 were significantly enhanced in larvae exposed to CAP. Recombinant PrTPX1 protein was expressed in Escherichia coli. Enzymatic assay revealed that the protein displayed antioxidant activity and was able to protect against oxidative challenge. These results indicated that PrTPX1 plays an important role in oxidative stress responses and may contribute to the CAP tolerance in SWB.

Predicting the effect of sirolimus on disease activity in patients with systemic lupus erythematosus using machine learning.

WHAT IS KNOWN AND OBJECTIVES: The present study aimed to predict the effect of sirolimus on disease activity in patients with systemic lupus erythematosus (SLE) using machine learning and to recommend appropriate sirolimus dosage regimen for patients with SLE. METHODS: The Emax model was selected for machine learning, where the evaluation indicator was the change rate of systemic lupus erythematosus disease activity index from baseline value. RESULTS: A total 103 patients with SLE were included for modelling, where the Emax , ET50 were -53.9%, 1.53 months in the final model respectively, and the evaluation of the final model was good. Further simulation found that the follow-up time to achieve 25%, 50%, 75% and 80% (plateau) Emax of sirolimus effecting on disease activity in patients with SLE were 0.51, 1.53, 4.59 and 6.12 months, respectively. In addition, the sirolimus dosage was flexible and adjusted according to drug concentration, where the intersection of sirolimus concentration range included in this study was about 8-10 ng/ml. WHAT IS NEW AND CONCLUSIONS: This study was the first time to predict the effect of sirolimus on disease activity in patients with SLE and in order to achieve better therapeutic effect maintaining a concentration of 8-10 ng/ml sirolimus for at least 6.12 months was necessary.

Quantifying the relationship between dapagliflozin and loss of weight in type 1 diabetes mellitus patients.

WHAT IS KNOWN AND OBJECTIVES: Dapagliflozin was the first oral treatment approved in type 1 diabetes mellitus (T1DM) patients, simultaneously improving body weight. However, the time course and dose effect of dapagliflozin on loss of weight in T1DM patients was still unknown. The present study aimed to investigate quantitative relationship between dapagliflozin and loss of weight in T1DM patients based on Model-based Meta-analysis. METHODS: Five dapagliflozin dosage groups, two of them were 5 mg/day and three of them were 10 mg/day, 1612 T1DM patients were analysed with maximal effect (Emax ) model, and evaluation index was change rate of body weight from baseline value. RESULTS: In these T1DM patients, dosages were not incorporated into model, indicating no significant dose-response relationship between 5 and 10 mg/day affecting loss of weight. Emax and the treatment duration to reach half of the maximal effects (ET50 ) of dapagliflozin influencing loss of weight in T1DM patients were -4.9% and 10.4 weeks, and the duration to achieve 25%, 50%, 75%, and 80% (plateau) of Emax were 3.5, 10.4, 31.2, and 41.6 weeks. WHAT IS NEW AND CONCLUSIONS: It was the first time to explore quantitative relationship between dapagliflozin and loss of weight in T1DM patients. To achieve the plateau period in loss of weight, 5 mg/day dapagliflozin was required for at least 41.6 weeks.

Optimization of initial dose regimen of tacrolimus in paediatric lung transplant recipients based on Monte Carlo simulation.

WHAT IS KNOWN AND OBJECTIVES: The initial tacrolimus dose regimen in paediatric lung transplant recipients is unknown. The present study optimized the initial tacrolimus dose regimen for paediatric lung transplant recipients. METHODS: This study was based on a published population pharmacokinetic model of tacrolimus in lung transplant recipients and used Monte Carlo simulations to recommend an initial dose regimen of tacrolimus in paediatric lung transplant recipients. RESULTS: Without voriconazole, the tacrolimus doses recommended for paediatric lung transplant recipients who were not CYP3A5*1 carriers were 0.02, 0.03, and 0.04 mg/kg/day, split into two doses, for weights of 10-16, 16-30, and 30-40 kg, respectively. For paediatric lung transplant recipients who were CYP3A5*1 carriers, the tacrolimus doses of 0.03, 0.04, 0.05, and 0.06 mg/kg/day, split into two doses, were recommended for weights of 10-16, 16-25, 25-30, and 30-40 kg, respectively. With voriconazole, the tacrolimus dose recommended for paediatric lung transplant recipients who were not CYP3A5*1 carriers was 0.02 mg/kg/day, split into two doses, for weights of 10-40 kg. For paediatric lung transplant recipients who were CYP3A5*1 carriers, tacrolimus doses of 0.02 and 0.03 mg/kg/day, split and two doses, were recommended for weights of 10-24 and 24-40 kg, respectively. WHAT IS NEW AND CONCLUSIONS: This study developed tacrolimus dose regimens for the first time for paediatric lung transplant recipients using Monte Carlo simulation and optimized initial dosage in paediatric lung transplant recipients.

Decision analysis of international joint prevention and control of public health emergencies.

COVID-19 has caused huge losses to countries around the world, and it will not end in a short time. The lack of motivation for international joint prevention and control is one of the important reasons for the global pandemic of COVID-19. How to improve the efforts and level of international joint prevention and control has become an urgent problem to be solved. Considering the long-term and dynamic nature of international joint prevention and control, the differential game method is used to compare and analyze the optimal decisions of countries in the three scenarios of spontaneous governance, external subsidies and internal cost sharing. The results show that the optimal prevention and control efforts of countries are negatively correlated with discount rates, prevention and control cost coefficients, decay rate and risk factors. It is positively correlated with the impact degree of social benefits, the impact degree of prevention and control efforts on the level of joint prevention and control, the distribution ratio of social benefits, and the impact degree of prevention and control level on social benefits. The prevention and control efforts, joint prevention and control level, social benefits and system benefits under spontaneous governance are the lowest and highest under the internal cost sharing. The internal cost sharing will only be carried out when social benefits distribution ratio obtained reach a certain threshold. This study provides decision-making support for the joint prevention and control of countries to defeat COVID-19 under the normalization of the epidemic.

Molecular characterization of a catalase gene from the green peach aphid (Myzus persicae).

The green peach aphid, Myzus persicae (Sulzer), is a serious agricultural pest with a worldwide distribution. Catalase (CAT), which is encoded by the catalase (Cat) gene, is an extremely important antioxidant enzyme that plays a pivotal role in protecting cells against the toxic effects of hydrogen peroxide. The Cat gene has not been characterized in M. persicae; therefore, this study describes the identification of the Cat (MpCat) gene from M. persicae. MpCat contains an open reading frame of 1515 bp and encodes a MpCAT protein consisting of 504 amino-acid residues. MpCAT possesses features typical of other insect catalases, including 7 conserved amino acids involved in binding heme and 15 involved in binding nicotinamide adenine dinucleotide phosphate. Phylogenetic analysis showed that MpCAT was closely related to orthologs from other aphid species. MpCat consisted of nine exons and eight introns, and the number and insertion sites of introns are consistent with those of Cat genes from Acyrthosiphon pisum (Harris) and Aphis gossypii Glover. The mRNA transcripts of MpCat were detected at all tested developmental stages, with the highest mRNA level in alate adults. The expression of MpCat was significantly upregulated when M. persicae was exposed to low and high temperatures, ultraviolet radiation, Beauveria bassiana, and permethrin. The transcription of MpCat and the activity of catalase were suppressed by RNA interference, and knockdown of MpCat significantly reduced the survival rate in M. persicae under heat stress. The results provide valuable information for further study on the physiological functions of MpCat.

Analysis of time course and dose effect of tacrolimus on proteinuria in lupus nephritis patients.

WHAT IS KNOWN AND OBJECTIVES: Tacrolimus is used to treat patients with lupus nephritis; however, its time course and dose effect on proteinuria in lupus nephritis patients remain unknown. The purpose of this study was to determine the time course and dose effect of tacrolimus on proteinuria in lupus nephritis patients via model-based meta-analysis (MBMA). METHODS: PubMed, Web of Science, Cochrane Library and ClinicalTrials.gov databases were systematically searched for information on the efficacy of tacrolimus against proteinuria in lupus nephritis patients. Useful data were extracted to build a model for the population studied using a non-linear mixed-effect model (NONMEM). This model was applied to simulate time course of tacrolimus on proteinuria using Monte Carlo simulations. RESULTS: Ten clinical studies that recruited 222 patients with lupus nephritis were included. Based on various diagnostic plots, we found that the established model described the observed data reasonably well. In addition, the typical Emax and ET50 of tacrolimus for 24-hour proteinuria in lupus nephritis patients were -5.88 g and 0.37 months, respectively. The baseline value of 24-hour proteinuria affected Emax . No significant dose-response relationship was observed in the range of tacrolimus concentration used in the present study (3-10 ng/mL), indicating that the effect of tacrolimus on proteinuria depends on effective concentration range and not the dose. However, the time course relationship was obvious; the efficacy of tacrolimus increased over time, reaching a plateau (80% Emax ) at approximately 1.48 months from the beginning of treatment. WHAT IS NEW AND CONCLUSION: When the concentration range of tacrolimus is maintained at 3-10 ng/mL, at least 1.48 months of treatment is required to achieve a better outcome with regard to proteinuria in lupus nephritis patients.

Inequity in inpatient services utilization: a longitudinal comparative analysis of middle-aged and elderly patients with the chronic non-communicable diseases in China.

BACKGROUND: Aging and the chronic non-communicable diseases (NCDs) challenge the Chinese government in the process of providing hospitalization services fairly and reasonably. The Chinese government has developed the basic medical insurance system to solve the problem of "expensive medical cost and difficult medical services" for vulnerable groups and alleviate the unfair phenomenon. However, few studies have confirmed its effect through longitudinal comparison. This study aimed to explore the trend in the inequity of inpatient use among middle-aged and elderly individuals with NCDs in China. METHODS: This longitudinal comparative study was based on CHARLS data in 2011, 2013 and 2015. Concentration index (CI) was used to measure the variation trend of inequity of inpatient services utilization, while the decomposition method of the CI was applied to measure the factors contributing to inequity in inpatient services utilization. The effect of each factor on the change of inequity in inpatient services utilization was divided into the change of the elasticity and the change of inequality using the Oaxaca-type decomposition method. RESULTS: The affluent middle-aged and elderly patients with NCDs used more inpatient services than poor groups. The per capita household consumption expenditure (PCE) and Urban Employee Basic Medical Insurance (UEBMI) contributed to the decline in pro-rich inequality of inpatient use, while the New Rural Cooperative Medical Scheme (NRCMS) contributed to the decline in pro-poor inequality of inpatient use. CONCLUSIONS: There was a certain degree of pro-rich unfairness in the probability and frequency of inpatient services utilization for middle-aged and elderly individuals with NCDs in China. The decrease of pro-wealth contribution of PCE and UEBMI offset the decrease of pro-poor contribution of NRCMS, and improved the equity of inpatient services utilization, favoring poor people.

Optimization of initial dosing scheme of tacrolimus in pediatric refractory nephrotic syndrome patients based on CYP3A5 genotype and coadministration with wuzhi-capsule.

The present study aimed to optimize the tacrolimus initial dosing scheme in pediatric refractory nephrotic syndrome patients based on population pharmacokinetics and pharmacogenomics.Demographic characteristics, concomitant medication, laboratory data, pharmacogenomics were collected to build the model and Monte Carlo was used to simulate the optimization of initial dosing scheme.Weight, the polymorphisms of CYP3A5, and concomitant medication of wuzhi-capsule were included into the covariates affecting tacrolimus clearance. In addition, with the same weight, there was difference in tacrolimus clearance in patients who carry CYP3A5*3/*3 and no coadministration of wuzhi-capsule, patients who carry CYP3A5*1 allele and no coadministration of wuzhi-capsule, patients who carry CYP3A5*3/*3 and coadministration of wuzhi-capsule, patients who carry CYP3A5*1 allele and coadministration of wuzhi-capsule, and their clearance ratios were 1:1.5:0.697:1.0455, respectively. Based on the differences of clearance in the above cases, we simulated different dosing regimens and obtained the optimal initial dose in each case.The present study recommended the tacrolimus initial dosing scheme in pediatric refractory nephrotic syndrome patients based on CYP3A5 genotype and coadministration with wuzhi-capsule.

Population pharmacokinetics and initial dosing regimen optimization of cyclosporin in pediatric hemophagocytic lymphohistiocytosis patients.

Hemophagocytic lymphohistiocytosis (HLH) is induced by various triggers, including genetic factors, infections, autoimmune diseases, lymphoma or other malignancies. Cyclosporin is one of the clinical treatments for HLH. However, cyclosporin has considerable inter- and intra-individual variabilities in pharmacokinetics and also displays a narrow therapeutic window, making it difficult to define an optimal dose for HLH treatment. This study is aimed to establish cyclosporin population pharmacokinetic (PPK) model of pediatric HLH patients and formulate an initial dose regimen for personalized medicine.Pediatric HLH patients between June 2014 and March 2019 from Children's Hospital of Fudan University were analyzed using NONMEM. Dose recommended was investigated using Monte Carlo simulations.The final cyclosporin PPK model was: CL/F = 91×(WT/70)0.75×(1+ Piperacillin-Tazobactam × Î¸P-T); V/F = 4250×(WT/70), where WT, and θP-T were weight, and the coefficient of the Piperacillin-Tazobactam, respectively. Based on the simulation results of our model, new initial dosage suggestions were recommended. In conclusion, the first cyclosporin PPK model in pediatric HLH patients was established and the model could be used to predict individualized initial dosing regimens in children with HLH.

Model extrapolation to a real-world dataset: evaluation of tacrolimus population pharmacokinetics and drug interaction in pediatric liver transplantation patients.

1. Numerous tacrolimus population pharmacokinetic (PPK) models in pediatric liver transplantation patients have been established to define an optimal dose schedule. However, the applicability of extrapolating these PPK models to our clinical center remains unknown. The goals of the present study was to evaluate model external predictiveness and establish a new model applicable to traditional therapeutic drug monitoring data.2. Published PPK models were collected from the literature and assessed using our real-world dataset including 41 pediatric liver transplantation patients via the individual prediction error method. The establishment of a new model was characterized using non-linear mixed-effects modeling.3. Nine published pediatric liver transplantation PPK models were identified, three of which could be applied to our real-world dataset. However, these models were dissatisfactory in terms of individual prediction error and hence, inadequate for extrapolation. Finally, a new model applicable to our real-world dataset was established as follows: CL/F = 22.9 × (WT/70)0.75 × (1 - WZ × 0.264) × (1 - FCZ × 0.338) × (1 + ASPI × 0.281) × (POD/41)0.0486 L/h; V/F = 906 × (WT/70) L. Where WT, WZ, FCZ, ASPI and POD were weight, Wuzhi capsule, fluconazole, aspirin and post-transplantation day, respectively. In conclusion, published models were inadequate for application to our real-world dataset. The present study produced a new model applicable to our real-world study data.

Association of Serum Complement C1q Concentration with Severity of Neurological Impairment and Infarct size in Patients with Acute Ischemic Stroke.

BACKGROUND: Inflammation occurs after acute ischemic stroke (AIS), and complement C1q is involved in inflammation. However, studies about the association of complement C1q with AIS are still rare. The aim of our study is to investigate the relationship between serum C1q concentration and the clinical severity of AIS. METHODS: A total of 1294 patients were enrolled in our study, including 647 patients with AIS and 647 non-stroke controls. The infarction volume of AIS was assessed by the diameter of maximum transverse section (DMTS) based on diffusion-weighted imaging (DWI) of brain magnetic resonance imaging. Neurological impairment was assessed by the National Institute of Health Stroke Scale (NIHSS). The association of serum C1q levels with DMTS or NIHSS was investigated by Pearson's or Spearman's correlation analysis. RESULTS: Serum C1q levels of patients with AIS were significantly higher than those of individuals without AIS. Serum levels of C1q were associated with DMTS (r=0.511, p<0.001) and NIHSS (r=0.433, p<0.001) among patients with AIS. CONCLUSION: Serum C1q concentration was positively associated with DMTS and NIHSS of patients with AIS.

Whole genome sequences reveal the presence of 11 heterotypic synonyms in the genus Sphingobium and emended descriptions of Sphingobium indicum, Sphingobium fuliginis, Sphingobium xenophagum and Sphingobium cupriresistens.

Phylogenetic analysis based on 16S rRNA gene sequences of the genus Sphingobium showed the presence of four distinguishable clusters, in each of which the species shared almost the same evolutionary distance. They were Sphingobium indicum, Sphinogbium lucknowense, Sphinogbium chinhatense, Sphinogbium francense and Sphinogbium japonicum in cluster I, Sphinogbium barthaii and Sphinogbium fuliginis in cluster II, Sphinogbium hydrophobicum and Sphinogbium xenophagum in cluster III and Sphinogbium czechense and Sphinogbium cupriresistens in cluster IV. The 16S rRNA gene sequence similarities between the species in each cluster were all higher than 98 %. Genome-based average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) relatedness values between the species of each cluster were all higher than the threshold values of 95-96 % ANI and 70 % dDDH for species discrimination, respectively, suggesting that each cluster represents only one species of the genus Sphingobium. Due to priority of publication, S. lucknowense, S. chinhatense, S. francense and S. japonicum should be taken as later heterotypic synonyms of S. indicum, S. barthaii as a later heterotypic synonym of S. fuliginis, S. hydrophobicum as a later heterotypic synonym of S. xenophagum and S. czechense as a later heterotypic synonym of S. cupriresistens. Correspondingly, the descriptions of S. indicum, S. fuliginis, S. xenophagum and S. cupriresistens are also emended based on this study.

Wuzhi capsule and haemoglobin influence tacrolimus elimination in paediatric kidney transplantation patients in a population pharmacokinetics analysis: A retrospective study.

WHAT IS KNOWN AND OBJECTIVES: Tacrolimus is widely used for kidney transplantation in children. However, the narrow therapeutic window and considerable interindividual and intraindividual variabilities make tacrolimus untoward to design an optimum dosage for paediatric personalized medicine. Our research aims to establish the tacrolimus population pharmacokinetics (PPK) of Chinese paediatric kidney transplantation patients and to distinguish covariates impacting variabilities. METHODS: Chinese paediatric kidney transplantation patients treated with tacrolimus between January 2014 and April 2018 from Children's Hospital of Fudan University were retrospectively analysed. A total of 51 Chinese paediatric kidney transplantation patients were analysed using non-linear mixed effects modelling (NONMEM). The effects of population characteristics, biological features and drug combination were assessed. The final PPK model was evaluated using visual inspection of routine diagnostic plots and the internal validation method of bootstrap. RESULTS: Our data met the condition of a one-compartment model, and the final model was CL/F = 32.7 × (WT/70)0.75  × (1 - WZ × 0.341) × (HGB/97)-0.508 ; V/F = 1890 × (WT/70) × (POD/57)0.816 , where WT, WZ, HGB and POD were weight, Wuzhi capsule (extracted from schisandra sphenanthera, whose primary efficient constituents are schisantherin A, schisandrol B, schisandrin etc, and often used to treat drug-induced hepatitis in Chinese organ transplant patients), haemoglobin and post-transplant day, respectively. WHAT IS NEW AND CONCLUSION: The tacrolimus PPK model in Chinese paediatric kidney transplantation patients was developed, and Wuzhi capsule and haemoglobin influence tacrolimus elimination in paediatric kidney transplantation patients.

[Clinical application evaluation and revision suggestions of clinical practice guideline on traditional Chinese medicine therapy alone or combined with antibiotics for sepsis].

To investigate the clinical application of clinical practice guideline on traditional Chinese medicine therapy alone or combined with antibiotics for sepsis, in order to promote the follow-up revision and further promotion of the Guidelines. Copies of 500 application evaluation questionnaire and 500 copies of applicability evaluation questionnaire were given to the clinicians who had used this Guideline in China, both in a form of registered questionnaire, and a database was established by Excel 2016 for descriptive statistical analysis. Copies of 211 application evaluation questionnaire and 211 copies of applicability evaluation questionnaire were collected. We can conclude from the survey that we should adjust the whole content and structure on the basis of better evaluation of the present recommendation scheme, update the prescription selection and clinical evidence of the recommendation scheme, and put forward the improvement measures for the hindrance factors in the application of the Guideline. Furthermore, in order to promote the Guideline more clearly, we should strengthen the doctor-patient education, improve guidance quality and increase the publicity, providing basis for the implementation and promotion strategies of the Guideline.

Genome-based reclassification of Sphingopyxis ummariensis as a later heterotypic synonym of Sphingopyxis terrae, with the descriptions of Sphingopyxis terrae subsp. terrae subsp. nov. and Sphingopyxis terrae subsp. ummariensis subsp. nov.

During the phylogenetic analysis of the genus Sphingopyxis, we found that an incorrect 16S rRNA gene sequence (accession number: D13727) was provided in the original description of Sphingopyxisterrae NBRC 15098T and the wrong sequence has been adopted and used for a long time. It should be replaced by the new correct 16S rRNA gene sequence (accession number: MF618306). The new sequence shared the highest similarity (99.8 %) with that of Sphingopyxisummariensis DSM 24316T. The average nucleotide identity (ANI) (96.87 %) and digital DNA-DNA hybridization (75.30 %) values based on the whole-genome sequences and almost the same phenotypic and chemotaxonomic characteristics of the two type strains revealed thatSphingopyxisummariensis should be a later heterotypic synonym ofSphingopyxisterrae. However, the distinctions in the genome size, hydrolysis of aesculin, α-glucosidase and particularly the fatty acid profiles strongly support that strain DSM 24316T should be considered to represent a novel subspecies ofSphingopyxisterrae. Two novel subspecies are therefore proposed, namely Sphingopyxisterraesubsp. terrae subsp. nov. (type strain E-1-AT=NBRC 15098T=JCM 10195T=DSM 8831T=LMG 17326T) and Sphingopyxisterraesubsp. ummariensis subsp. nov. (type strain UI2T=DSM 24316T=CCM 7428T=MTCC 8591T).